This invention relates to Nuclear Magnetic Resonance (NMR) and Positron Emission Tomography(PET) scanner apparatus and more particularly, to scanner apparatus for performing both NMR and PET scanning and yielding improved spatial resolution of a PET image by achieving PET scanning in a magnetic field. The magnetic field is preferably made available by virtue of the NMR apparatus associated with the combined scanner.
The NMR phenomenon, which is now well known, can be employed to map tissue structure and measure biochemical pathways of compounds labelled with NMR active nuclei. For example, such techniques may be utilized to measure the metabolic pathway of C-13 enriched glucose in tissue. Other applications such as the detection of cancerous cells, as well as neurological applications, are well known.
The NMR phenomenon can be detected in materials that have isotopes with a net nuclear spin i.e., H-1, H-2, C-13, P-31, F-19. Thus, in the presence of an externally applied magnetic field the energy levels of these nuclei are no longer degenerate. Radiofrequency pulses are typically employed to stimulate transitions between energy levels. The nuclei that have a spin of one half have only two nuclear energy levels. Thermodynamics imposes a larger spin population for the lower energy state relative to the higher energy state. When the spin states are in thermal equilibrium, the population ratio between the upper and lower energy states is defined by Boltzman's equation EQU N.sup.+ /N.sup.- =EXP (-.DELTA.E/kT)
where:
N.sup.+, N.sup.- =population upper and lower energy states, respectively PA1 .DELTA.E=energy difference between spin states (J) PA1 k=Boltzman's constant (J/.degree.K.) PA1 T=spin temperature (.degree.K.) PA1 w=frequency (rad/s) PA1 .gamma.=gyromagnetic ratio (rad/T-s) PA1 B=magnetic field (T) PA1 H=proton PA1 .beta..sup.+=positron PA1 .sub.o.sup.1 n=neutron PA1 .nu.=neutrino
An RF pulse is generally utilized to stimulate transitions between energy levels. The frequency of radiation necessary to induce these transitions is defined by the Larmor equarion: EQU w=.gamma.B
where:
Due to the excess spin population in the lower energy levels, more spins are transferred to the upper energy state than to the lower energy state during the presence of an RF pulse. Thus, the sample has a net absorption of RF energy. Due to molecular motions in the sample, spins in the higher energy levels are stimulated to transition to the lower energy levels and this process leads to the re-emission of absorbed RF energy which may typically be detected with a small signal amplifier. Spatial information can be obtained when time varying magnetic field gradients are employed during an NMR experiment. Chemical information naturally arises from the detected NMR signal because different configurations and conformations of molecules containing NMR active nuclei give rise to a range of NMR frequencies.
NMR imaging and spectroscopy has been applied to a number of medical and non-medical applications. In biological systems, the most commonly studied nucleus is the proton. This is because protons are the most abundant nuclei in tissue, possess the highest NMR sensitivity of any other nucleus with the exception of tritium, and have favorable spin-lattice and spin-spin relaxation times. Images of other nuclei in biological systems have been made, i.e., C-13, Na-23, P-31. These images are typically characterized by smaller gyromagnetic ratios, unfavorable relaxation times and metabolite concentrations being 1000 times smaller than water concentrations. Thus, the spatial resolution of images acquired from such nuclei are typically courser because of signal-to-noise and gradient strength considerations.
Tissue chemistry can also be studied by NMR spectroscopic techniques. Spatial localization of NMR spectra is possible for the more abundant nuclei such as H-1 and P-31. However, spatial localization of labelled metabolites such as C-13 enriched glucose and its C-13 labelled metabolic intermediates is possible but more difficult. This is especially so if C-13 labelled metabolites are in tissues which cannot be accessed by surface coils such as tissues deep within the brain. Thus, localized NMR spectroscopy of tagged molecules is difficult because of low signal to noise ratios. If an NMR labelled molecule could also be tagged with a positron emitter, i.e., C-11, a PET image would show the site of metabolism.
PET measures the spatial distribution of positron emitting radionuclides in an object. This is done by detecting annihilation photons from compounds labelled with positron emitting isotopes. Positrons are emitted from isotopes that have a low neutron to proton ratio or conversely, a high proton to neutron ratio. Thus, in order to achieve nuclear stability, a proton decays into a neutron, positron, and neutrino according to the formula: EQU H.fwdarw..beta..sup.+ +.sub.0.sup.1 n+.nu.
where:
Positrons hava a continuum of energies ranging from O MeV to E.sub.max, where E.sub.max can correspond to a few MeV. Each positron emitting radionuclide has a unique distribution of positron energies. An emitted positron gradually loses its kinetic energy as it travels through matter. This kinetic energy is degraded by ionization and excitation interactions with orbital electrons of the atoms the positron passes. When a positron has lost most of its energy, it will combine with an electron to form a metastable positronium atom before the positron and electron mutually annihilate one another. As a result of the annihilation, the mass of the electron and positron are transformed into two 0.511 MeV photons which are emitted and travel in opposite directions.
It is precisely this radiation that a PET scanner is designed to detect. Thus, coincident detection of annihilation photons by a pair of radiation detectors, 180.degree. apart, places the photons on a line through the sample. Time of flight measurements may be employed to localize the event to a small portion of the line.
However, resolution of a PET image is determined by extrinsic and intrinsic factors. Collimation, efficiency, and time resolution of the radiation detector provides the extrinsic limit of resolution which is approximately 1-2 mm. The distance a positron travels through matter before annihilation limits the intrinsic resolution of PET. While improvements in detector design and computer algorithms can usually improve the extrinsic resolution limit, the intrinsic resolution limit of PET imaging is generally only variable by utilizing radioisotopes having different positron energies. The smaller the position energy, the less a positron needs to travel before annihilation occurs and this will result in higher resolution. However, the method of employing radioisotopes having different positron energies is generally of limited use if compounds need to be labelled with specific positron emitting nuclides. A major weakness of PET is that it cannot depict tissue morphology or the metabolic fate of the labelled compound.
It has been determined that merging NMR and PET techniques into one device simultaneously enhances the strengths of each technique while minimizing their respective limitations. For example, H-1 NMR images provide structural information on the region of interest that PET is scanning. Further, NMR spectra of isotopically enriched metabolites, i.e. C-13, F-19, would delineate biochemical pathways. PET images of metabolites labelled for NMR studies and also tagged with a positron emitter would show the location of regional metabolism. In addition, in-plane resolution of PET images would be enhanced in a magnetic field. See for example, A Simulation Study of a Method to Reduce Positron Annihilation Spread Distribution Using a Strong Magnetic Field in Positron Emission Tomography, H. Iida, I. Kanno, S. Miura, M. Murakami, K. Takahashi, and K. Uemura, IEEE Transactions on Nuclear Science, Vol. 33, 1, Feb. 1986, pp. 597-600. Thus, while this article indicates at page 599, that the required magnetic field to reduce the spread of positron annihilation is terribly high, for practical PEt devices it has been determined that the field strengths available in NMR devices are appropriate to achieve a marked reduction in the spread of positron annihilations and to significantly improve the resolution of PET scanner according to the present invention.
The combination of NMR and PET scanning techniques within a scanner device, while providing theoretical enhancements of each techhique, imposes design constrains which are extremetly onerous and might be considered to mandate the mutual exclusivity of each approach. More particularly, PET scanners normally employ photomultiplier tubes as part of their photon detection instrumentation. Photomultiplier tubes, in turn, do not function very well in magnetic fields and conversely, the magnetic field homogeneity which is mandatory in NMR operation is distored by ferromagnetic PMT assemblies. It has been determined that these problems may be overcome by coupling scintillation crystals to a rack of photomultiplier tubes through quartz light pipes and magnetically shielding the photomultiplier tube assembly once the same is located a suitable distance from the magnet. However some loss in efficiency of photon detection will occur with this approach. Alternatively ceramic or similar other detection crystals can be coupled to a photodiode. This eliminates the shielding requirements imposed upon systems designed with photomultipliers. Similarly superconducting colloidal detectors could also be used, here a photomultiplier tube is not required. These devices depend upon having a magnetic field for their operation. This field may be supplied by the NMR imaging magnet.
Therefore, it is a principal object of the instant invention to provide combined NMR-PET scanner apparatus. Various other objects and advantages of the present invention shall become clear from the following detailed description of an exemplary embodiment thereof and the novel features will be particularly pointed out in conjunction with the claims appended hereto.